Fluorescent tagging of cells using dyes, fluorescent proteins, and quantum dots forms the basis for many powerful analytical methods in modern biology. Locating these cells within entire animals is necessary to study cell delivery, differentiation and gene expression. The Phase II SBIR research is developing an intelligent microtome to provide the means to locate cells within an intact organ or organism and to capture thin sections containing target cells. This instrument will serially section whole organs or small mammals, record multiple wavelength fluorescence images from the tissue after removal of each section, analyze changes in fluorescent patterns in real time, and automatically collect thin sections from areas where fluorescently tagged cells are present. The compact instrument will mount on a typical laboratory bench. Instruments will be constructed for testing in university research laboratories studying gene therapy, stem cell behavior, pulmonary dysfunction, and gene transfer by bacterial transfection. A niche analysis of the commercial market for the intelligent microtome was performed during Phase I. The analysis indicated broad interest in this low-cost approach to three- dimensional imaging and the selective automated approach to collection of thin sections. PUBLIC HEALTH RELEVANCE: New biomedical methods are being designed to deliver DNA, RNA, or stem cells to targeted locations within the body to treat disease conditions. The research described in this Phase II SBIR proposal will manufacture intelligent microtomes, based upon prototype development studies conducted in Phase I. These new instruments will be evaluated in university research laboratories for their capability to section and image entire research animals, to locate stem cells or cells in which DNA or RNA is expressed, and to collect those cells in thin sections for further examination. This research will help the answer the questions "Which cells within the entire organism are affected by the gene or stem cell therapy?" and "What is going on at a biochemical level within these cells?"